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Neoadjuvant letrozole and palbociclib in patients with HR-positive/HER2-negative early breast cancer and Oncotype DX
Á Guerrero-Zotano1, J M Pérez-García2, M Ruiz-Borrego3
1lnstituto Valenciano de Oncología, Valencia.
Background:
The effect of the addition of cyclin-dependent kinases 4 and 6 inhibitors to endocrine therapy in terms of molecular downstaging remains undetermined. Switching from a high-risk to a low risk Recurrence Score (RS) group could provide useful information to identify patients who might not require chemotherapy. The purpose of this study was to assess the biological and clinical activity of letrozole plus palbociclib as neoadjuvant treatment for patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with an initial Oncotype DX RS ≥18.
Patients And Methods:
Participants were women aged ≥18 years with HR-positive/HER2-negative, Ki67 ≥ 20%, stage II-IIIB early breast cancer with a baseline RS ≥18. Eligible patients with a pretreatment RS 18-25 (cohort A) and 26-100 (cohort B) received six 28-day cycles of letrozole (2.5 mg per day; plus goserelin if pre- or perimenopausal) plus palbociclib (125 mg per day; 3/1 schedule) before surgery. The primary endpoint for both cohorts was the proportion of patients who achieved an RS ≤25 at surgery or a pathological complete response (pCR).
Results:
A total of 67 patients were enrolled, among which 65 were assessable for the primary endpoint (32 patients in cohort A and 33 in cohort B). At surgery, 22 (68.8%) patients in cohort A and 18 (54.5%) patients in cohort B had an RS ≤25 or a pCR [only 1 (3.0%) patient in cohort B], meeting the primary endpoint in cohort B (P < 0.01), but not in cohort A (P = 0.98). No new safety signals were identified.
Conclusions:
The efficacy of neoadjuvant treatment with letrozole plus palbociclib does not seem to depend on pretreatment RS for patients with RS ≥18. However, around half of patients with HR-positive/HER2-negative early breast cancer with an RS 26-100 at baseline achieved molecular downstaging with this regimen.
Insights
Neoadjuvant letrozole plus palbociclib showed efficacy in downstaging early breast cancer, particularly in patients with higher Recurrence Score (RS) values. This treatment helps identify patients who may not need chemotherapy, improving personalized treatment strategies.
Area of Science:
- Oncology
- Pharmacology
- Genomics
Background:
- The role of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors in endocrine therapy for molecular downstaging in early breast cancer is under investigation.
- Identifying patients who can avoid chemotherapy based on Recurrence Score (RS) group shifts is crucial for personalized treatment.
Purpose of the Study:
- To evaluate the biological and clinical activity of neoadjuvant letrozole plus palbociclib.
- To assess treatment efficacy in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with an initial Oncotype DX RS ≥18.
Main Methods:
- A study involving women with HR-positive/HER2-negative early breast cancer and a baseline RS ≥18.
- Patients received six cycles of letrozole plus palbociclib before surgery.
- The primary endpoint was achieving a postsurgical RS ≤25 or a pathological complete response (pCR).
Main Results:
- 67 patients were enrolled; 65 were assessable.
- The primary endpoint was met in cohort B (RS 26-100) with 54.5% achieving RS ≤25 or pCR (P < 0.01).
- Cohort A (RS 18-25) did not meet the primary endpoint (P = 0.98), with 68.8% achieving RS ≤25 or pCR.
Conclusions:
- Neoadjuvant letrozole plus palbociclib efficacy for molecular downstaging appears independent of pretreatment RS in patients with RS ≥18.
- Approximately half of patients with HR-positive/HER2-negative early breast cancer and an RS 26-100 at baseline achieved molecular downstaging.
- No new safety concerns were identified with this neoadjuvant regimen.
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